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Antagonism of Ca 2+ and other actions of verapamil in guinea‐pig isolated trachealis
Author(s) -
Foster R.W.,
Okpalugo B.I.,
Small R.C.
Publication year - 1984
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1984.tb10103.x
Subject(s) - trachealis muscle , verapamil , chemistry , tetrodotoxin , acetylcholine , medicine , tetraethylammonium chloride , histamine , endocrinology , calcium , tetraethylammonium , potassium , charybdotoxin , organic chemistry
1 In trachealis bathed by a K + ‐rich, Ca 2+ ‐free physiological salt solution, calcium chloride (CaCl 2 ) at 0.01 to 10 mmol l −1 evoked concentration‐dependent spasm. Verapamil (0.1 to 10 μmol l −1 ) was an effective antagonist of CaCl 2 . 2 Spasm evoked by acetylcholine, histamine, potassium chloride (KCl) and tetraethylammonium (TEA) was studied in trachealis bathed by normal Krebs solution. Verapamil (0.1 to 10 μmol l −1 ) markedly suppressed spasm evoked by KCl and TEA. In contrast the actions of acetylcholine and histamine were much less affected by verapamil. 3 Spasm evoked by prostaglandin E 2 was studied in trachealis bathed by Krebs solution containing indomethacin (2.8 μmol l −1 ). Verapamil (0.1 to 10 μmol l −1 ) had little or no effect against prostaglandin E 2 ‐induced spasm. 4 Verapamil (0.1 to 10 μmol l −1 ) had relatively little effect on the tone of trachealis bathed by normal Krebs solution. In contrast bathing in Krebs solution lacking CaCl 2 caused almost complete tone loss. 5 Extracellular electrophysiological recording showed that verapamil (10 μmol l −1 ) suppressed not only TEA‐evoked spasm but also TEA‐evoked slow waves and spike potentials. Verapamil also abolished the transient period of slow wave activity associated with the spasm evoked by KCl. 6 Intracellular electrophysiological recording showed that TEA‐induced spike activity was resistant to tetrodotoxin (3 μmol l −1 ). However, verapamil (10 μmol l −1 ) abolished the tetrodotoxin‐resistant spikes without increasing the resting membrane potential. 7 It is concluded that verapamil suppresses TEA‐ or KCl‐induced spasm, slow waves or spikes by inhibition of Ca 2+ influx. Spasm evoked by acetylcholine, histamine and prostaglandin E 2 depends on mechanisms for increasing the cytoplasmic concentration of free Ca 2+ which are resistant to verapamil. The failure of verapamil markedly to depress tissue tone is consistent with the proposal that tone results from the activity of endogenous prostaglandins.